1. Field of the Invention
This invention relates generally to the field of drug, bio-affecting and body treating compositions, and more specifically to physiologically acceptable astringents for use in selectively controlling the exocrine function of the testes in the production of sperm and the endocrine function in the production of testosterone.
2. Description of the Prior Art
A large number and variety of chemical approaches have been tried to affect spermatogenesis in male animals. These approaches have included luteinizing hormones, testosterones, steroids and other steroidal derivatives. Examples of such compounds are described in U.S. Pat. No. 3,836,640.
In nearly all of these prior approaches, the compounds have been administered orally or injected into the body. None have proved chemically or commercially successful. Nearly all have failed because of adverse side effects or reduction of libido.
The spermicidal effects of many non-essential metals are also known and have been comprehensively reported. Gunn, Samuel A. and Thelma Clarke Gould, 1970, The Testis, Vol. III, Influencing Factors, 377-481. Many of the metals studied are normally considered as toxic in any form.
The presence of zinc in the male reproduction process is well established, but its mode of action is not clearly defined. Human seminal plasma normally contains a high concentration of zinc. Gallob-Hausmann, Gerda, Zinc and Its Physiological Relationship to the Human Body--A Review. However, there are indications that zinc ions under certain conditions can exert toxic effects on human spermatozoa. White, I. G., 1955, The Toxicity of Heavy Metals to Mammalian Spermatozoa, Austral. J. Exp. Biol. 33, 359-366. Rosado, A., et al. 1970, Inhibition of Human Sperm Motility by Calcium and Zinc Ions, Contraception 2, 259-273. Kesseru, E., et al. 1972, Influence of Metals in In Vitro Sperm Migration in the Human Cervical Mucus, Contraception 6, 231-240.
Zinc evidently plays a role in reproduction, appearing with carbonic anhydrase and alkaline phosphatase in the prostate and testes. The amount of zinc found in this tissue, however, is much higher than would normally be associated with the amount of these two enzymes present. Despite the large number of experiments demonstrating the presence and behavior of zinc in the male sex accessory organs, the function of this metal remains obscure. Byar, David P., 1974, Zinc in Male Sex Accessory Organs: Distribution and Hormonal Response, Chapt. 6, Male Accessory Sex Organs--Structure and Function in Mammals.
The toxic effects of zinc ions on human spermatozoa in vitro have also been studied. Lindholmer, C. 1974, Toxicity of Zinc Ions to Human Spermatozoa and the Influence of Albumin, Andologia 6 (1), 7-16. The purpose of this study was to analyze the effects of zinc on the motility and survival of human spermatozoa, and to what extent these effects could be modified by albumin. Collected sperm cells were separated from the seminal fluid by centrifugation and washed in a special solution. The washed cells were divided into two sample groups and 4% human albumin added to one group. A total concentration of 4% albumin was chosen because this corresponds to the total protein concentration of human seminal fluid.
The test results showed that the addition of zinc at a concentration of 5 .mu.g/ml (0.075 mM) to the samples without albumin markedly inhibited sperm motility. By contrast, the addition of zinc at a concentration of 50 .mu.g/ml (0.75 mM) to the samples containing 4% albumin only slightly inhibited sperm motility. The protective effect of the albumin thus was clearly demonstrated.
It is presumed that with the concentration of albumin and zinc normally present in human semen, zinc albumin complexes are formed, some of which may precipitate on the cell surfaces. The biological significance of such precipitate and coating complex is not known, but is assumed to be of importance for protecting the cells against toxic substances in the seminal fluid.